Clinical Presentation and 28-Day Mortality in Hospitalized Neonates and Young Infants with Clinical Sepsis: The Global NeoOBS Observational Cohort

Background: There are limited data on sepsis management and outcomes in neonates and young infants in low- and middle-income countries (LMIC) to inform antibiotic trials in settings of high resistance.Methods: The NeoOBS study enrolled infants <60 days, presenting with sepsis (≥2 sepsis criteria) across 19 sites in 11 countries predominantly in LMIC, with prospective data collection, including baseline clinical features and pathogens, and mortality through 28 days. A multivariable Cox regression model was built to predict 28-day mortality and develop a sepsis severity score in a randomly selected 85% of infants, validated in the remaining 15%.Findings: 3204 infants with median age 5 days (IQR 2-15), birth weight 2500g (1400-3000g), and 4 clinical (2-5) and 1 laboratory (0-2) signs were enrolled between 2018-2020. Overall mortality was 11.3% (95%CI 10.2-12.5%; n=350), higher in infants with culture-positive sepsis (17.7% (14.7-21.1%) n=564). Among 309 infection-related deaths, 59.2% (n=183) were healthcare-associated infections (HAI). Klebsiella pneumoniae was the most common pathogen (n=132, 23.4% of positive cultures). Empiric antibiotics varied widely, with high carbapenem use. A neonatal sepsis severity score based on infants’ characteristics, supportive care, and clinical signs had validation sample mortality (95%CI) of 0% (0-3%), 8% (6-12%), and 27% (18-39%) in low (score 0-3), medium (4-6) and high (7-14) risk groups, respectively. The score performed similarly across subgroups of preterm/term infants and early/late-onset sepsis.Interpretation: Mortality, HAI, and carbapenem use are high in neonatal units globally. Alongside prevention, strategic treatment trials are required, which can be facilitated using the NeoSep Severity Score based entry criteria.Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03721302).Funding: The study was sponsored by the Global Antibiotic Research and Development Partnership (GARDP) with additional funding from: Bill and Melinda Gates Foundation, German Federal Ministry of Education and Research (BMBF), South African Medical Research Council, UK Department of Health and Social Care, Monaco and in-kind contribution from Indian Council for Medical Research.Declaration of Interest: None to declare. Ethical Approval: Ethical approval was obtained from St. George’s, University of London (SGUL) Research Ethics Committee